Table 1.

Table showing the Nutraceuticals used in the management of knee osteoarthritis, their source, active ingredient, mechanism of action and side effects.

Nutraceuticals	Source	Active ingredient	Mechanism of action	Side effects
Boswellia	Boswellia serrata gum resin	3-O-Acetyl-11-keto-beta-boswellic acid18	Inhibit 5-lipoxygenase,18 inhibit complement system at the level of conversion of C3 in to C3a and C3b, also inhibit proinflammatory cytokines17	Gastrointestinal symptoms17
Aflapin	Synergistic composition of Boswellia serrata extract enriched in AKBA and non-volatile oil portion of B.serrata gum resin29	AKBA	5-lipoxygenase inhibition and Matrix Metalloproteinase 3 inhibition26	Nausea and Headache
Glucosamine	Glucosamine can be extracted from the chitosan and chitin exoskeleton of crustaceans such as shelfish and can be stabilized by salt32	Glucosamine Sulfate, Glucosamine Hydrochloride	GlcN penetrates into cells by means of glucose transporters. GlcN associate to O-GlcNAcylate proteins and modulates their activity, e.g. decrease nuclear factor-κB nuclear translocation. GlcN may also affect the transcription of pro-inflammatory cytokines by epigenetic mechanisms.34	Shelfish allergy,36,37 Affect glucose metabolism and can induce insulin resistance,35 Administered as a salt: Na+ and CL- can affect blood pressure and renal function in those pt.36,37
Chondroitin	Can be obtained from shark or bovine cartlige33	Chondroitin 4 and 6 sulfate	CS do not penetrate into chondrocytes, synoviocytes, and elicit the anti-inflammatory effect by engaging membrane receptors, e.g. CD44, TLR4, and ICAM1, with a resulting dual effect: impede the fragments of extracellular matrix engaging these receptors, cause of inflammatory reaction, and block the signal transduction pathways activated by the fragments and so diminish the nuclear translocation of pro-inflammatory transcription factors.34	Epigastric pain, diarrhea, heart burn, nausea38
Collagen peptide	Derived from gelatinization and subsequent enzymatic hydrolysis of native collagen and it contains small peptide with a molecular weight lower than 5000 Da53	Collagenic animal tissue53	Stimulates collagenic tissue regeneration by increasing collagen synthesis, glycosaminoglycans and hyaluronic acids53
Curcumin	Curcumin is derived from turmeric, a popular spice used in India, South Asia, and Japan, which is the grounded root and rhizome of the plant Curcuma Longa58,59	Curcumin	Suppression of NF-kappaB mediated IL-1beta/TNF-alpha catabolic signaling pathways in chondrocytes60,61	Dyspepsia, abdominal pain, nausea, loose stool67
Fish Oil	Obtained from the body of fatty fish75	n-3fatty acids, eicosapentaenoic acid, docosahaexaenoic acid75	Dose dependant decrease in inflammatory destruction of cartilage tissue75	Intolerance, diarrhea and gastroesophageal reflux76
Ginger	Ginger is rhizome of Z.officinale		Reduces inflammatory markers like nitric oxide, hs-C reactive protein,81 TNF-alpha and IL-1beta82
Green tea		Polyphenols: epigallocatechin-3-gallate88	Inhibit expression of TNF alpha, MMP-13 and NF-kappaB, inhibit IL-1beta90,91 and modulate miRNAs expressions92
Rose Hip Extract	RHP, prepared from dried Rosa canina fruitsof a selected cultivar, obtained from Hyben Vital, Langeland, Denmark.94	galactolipid (2 S)-1,2-di-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O-beta-d-galactopyranosyl glycerol95	Proposed M/A: Rose hip extract inhibited the chemotaxis and chemiluminescence of peripheral blood polymorphonuclear leucocytes and also reduces the level of serum creatinine and acute phase protein CRP96